Multitubular enzyme reactors were prepared with immobilized phenylalanine ammonia lyase (PAL), an enzyme which metabolizes phenylalanine to transcinnamic acid and ammonia. Such enzyme reactor reduced phenylalanine levels in vitro, in human blood and in vivo in animals with experimental phenylketonuria without affecting circulating blood elements or the level of BUN. In order to increase in vivo efficiency we will develop enzyme reactors with a new type of fiber (BPD) and with a PAL-enzyme prepared in our laboratory. These reactors will be studied for permeability and stability. One criterion of stability is lack of immunologic response to the immobilized PAL. This will be tested with a battery of immunological methods, adapted to animal sera. Stability of enzyme reactor will also be tested using various methods of sterilization in preparation for eventual clinical use. For the simultaneous determination of phenylalanine, tyrosine, transcinnamic acid and trans-coumaric acid a new analytical method will be developed employing High Pressure Liquid Chromatography. To avoid thrombogenicity and eventually eliminate heparinization, we will work on developing immobilization of streptokinase and urokinase on tubular structures. Fibers available so far did not retain these activators in a stable form. With the new fibers available we have hope for increased stability of immobilization, with retention of high plasminogen activator activity.